Effect of Spermidine on Misfolding and Interactions of Alpha-Synuclein

• DOI: 10.1371/journal.pone.0038099
• Publication Date: 2012-05-25T21:43:34Z
• Authors: Alexey V. Krasnos...; Jie Peng; Josephat M. Asiago; Jagadish Hindupur; Jean-Christophe R...; Yuri L. Lyubchenko
• Keywords: Microscopy; Protein Folding; 0303 health sciences; Spermidine; Science; Q; R; Atomic Force; Pharmacy and Pharmaceutical Sciences; Microscopy, Atomic Force; 03 medical and health sciences; alpha-Synuclein; Medicine; Humans; Protein Multimerization; Research Article

Alpha-synuclein (α-Syn) is a 140 aa presynaptic protein which belongs to group of natively unfolded proteins that are unstructured in aqueous solutions. The aggregation rate α-Syn accelerated the presence physiological levels cellular polyamines. Here we applied single molecule AFM force spectroscopy characterize effect spermidine on very first stages – misfolding and assembly into dimers. Two variants, wild-type (WT) A30P, were studied. two molecules covalently immobilized at C-terminus, one tip other substrate, intermolecular interactions between measured by multiple approach-retraction cycles. At conditions close ones rare event, addition leads dramatic increase propensity WT mutant misfold. Importantly, characterized set conformations, A30P changes pattern as well strength interactions. Together with fact facilitates late aggregation, our data demonstrate promotes early including dimerization. This finding suggests increased potentially polyamines can initiate disease-related process α-Syn.